Cell-autonomous transcriptional mechanism for enhancement of translation capacity in secretory cells

BioRxiv : the Preprint Server for Biology
Konstantin KhetchoumianJacques Drouin


Translation is a basic cellular process and its capacity is adapted to cell function. In particular, secretory cells achieve high protein synthesis levels without triggering the protein stress response. It is unknown how and when translation capacity is increased during differentiation. Here, we show that the transcription factor Creb3l2 is a scaling factor for translation capacity in secretory cells and that it directly binds ~75% of regulatory and effector genes for translation. In parallel with this cell-autonomous mechanism, implementation of the physiological UPR pathway prevents triggering the protein stress response. The pituitary differentiation factor Tpit activates Creb3l2 expression, the Creb3l2-dependent regulatory network as well as the physiological UPR pathway. Thus, Creb3l2 implements high basal translation levels through direct targeting of translation effector genes acting downstream of signaling pathways that otherwise regulate protein synthesis. Expression of Creb3l2 may be a useful means to enhance production of therapeutic proteins.

Related Concepts

Cell Differentiation Process
Signal Pathways
Transcription Factor
Transcription, Genetic
Biological Adaptation to Stress
Immune Effector Cell
Protein Biosynthesis
Therapeutic protein

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